Transcriptional mutagenesis mediated by 8-oxoG induces translational errors in mammalian cells.

Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is suppressed. Using second-generation sequencing techniques, we found that U-to-G changes at preassigned sites of the luciferase transcript increased when 8-oxoGTP was supplied. In addition, an increased level of 8-oxoG content in RNA induced the accumulation of aggregable amyloid ß peptides in cells expressing amyloid precursor protein. Our findings indicate that 8-oxoG accumulation in mRNA can alter protein synthesis in mammalian cells. Further work is required to assess the significance of these findings under normal physiological conditions.

Effect of Chinese herbal compound Naofucong () on the inflammatory process induced by high glucose in BV-2 cells.

OBJECTIVE: To determine the effect of medicated serum of Chinese herbal compound Naofucong (, NFC) on the microglia BV-2 cells viability and the transcription and expression of interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) in microglia BV-2 cells to further explore the mechanisms underlying the protective effect of NFC on inflammatory process induced by high glucose. METHODS: The microglia BV-2 cells incubated in vitro were divided into different groups: the control group (25 mmol/L glucose), the model group (75 mmol/L glucose), high glucose media containing different dose medicated serum of NFC. After being cultured for 24 h, changes in IL-6 and TNF-α were measured by quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. The expression of surface marker CD11b of activated microglia was measured by confocal laser scanning microscope and Western blot. Nuclear factor-κB (NF-κB) p-p65 expression was analyzed by Western blot. RESULTS: The model group obviously increased the expression of microglial surface marker CD11b and NF-κB p-p65 (all P<0.01), induced a signifificant up-regulation of release and the mRNA expression of IL-6 and TNF-α (P<0.01 or P<0.05). The medicated serum of NFC could obviously down-regulate the transcription and expression of surface marker CD11 b and NF-κB p-p65 (all P<0.01), and inhibit the mRNA and protein expression (P<0.01 or P<0.05) of inflflammatory cytokines, such as IL-6 and TNF-α, in microglia BV-2 cells cultured with high glucose for 24 h. CONCLUSIONS: The inhibition of microglial activation and IL-6 and TNF-α expression induced by high glucose may at least partly explain NFC therapeutic effects on diabetes-associated cognitive decline diseases. Its underlying mechanism could probably be related to the inhibition of NFC on NF-κB phosphorylation.

M2 Macrophage Transplantation Ameliorates Cognitive Dysfunction in Amyloid-ß-Treated Rats Through Regulation of Microglial Polarization.

Alzheimer's disease (AD) is the most common neurodegenerative disorder in the elderly population. Neuroinflammation induced by amyloid-ß (Aß) aggregation is considered to be the critical factor underlying AD pathological mechanisms. Alternatively activated (M2) macrophages/microglia have been reported to have neuroprotective effects in neurodegenerative disease. In this study, we characterized the neuroprotective effects of M2 macrophage transplantation in AD model rats and investigated the underlying mechanisms. Intracerebroventricular injection of Aß1 - 42 to rats was used to model AD and resulted in cognitive impairment, neuronal damage, and inflammatory changes in the brain microenvironment. We observed an increased interferon regulatory factor (IRF) 5/IRF4 ratio, resulting in greater production of classically activated (M1) versus M2 microglia. M2 macrophage transplantation attenuated inflammation in the brain, reversed Aß1 - 42-induced changes in the IRF4-IRF5 ratio, drove endogenous microglial polarization toward the M2 phenotype, and ameliorated cognitive impairment. Nerve growth factor (NGF) treatment reduced the IRF5/IRF4 ratio and induced primary microglial polarization to the M2 phenotype in vitro; these effects were prevented by tyrosine Kinase Receptor A (TrkA) inhibition. M2 macrophage transplantation restored the balance of IRF4-IRF5 by affecting the expression of NGF and inflammatory cytokines in the brains of AD model rats. This drove microglial polarization to the M2 phenotype, promoted termination of neuroinflammation, and resulted in improved cognitive abilities.

Lactulose enhances neuroplasticity to improve cognitive function in early hepatic encephalopathy.

Lactulose is known to improve cognitive function in patients with early hepatic encephalopathy; however, the underlying mechanism remains poorly understood. In the present study, we investigated the behavioral and neurochemical effects of lactulose in a rat model of early hepatic encephalopathy induced by carbon tetrachloride. Immunohistochemistry showed that lactulose treatment promoted neurogenesis and increased the number of neurons and astrocytes in the hippocampus. Moreover, lactulose-treated rats showed shorter escape latencies than model rats in the Morris water maze, indicating that lactulose improved the cognitive impairments caused by hepatic encephalopathy. The present findings suggest that lactulose effectively improves cognitive function by enhancing neuroplasticity in a rat model of early hepatic encephalopathy.

Neuroprotective effects of Aceglutamide on motor function in a rat model of cerebral ischemia and reperfusion.

PURPOSE: To investigate the effect and underlying mechanism of Aceglutamide on motor dysfunction in rats after cerebral ischemia-reperfusion. METHODS: Adult male Sprague-Dawley rats were subjected to 2 h transient middle cerebral artery occlusion (MCAO). Aceglutamide or vehicle was intraperitoneally given to rats at 24 h after reperfusion and lasted for 14 days. Subsequently functional recovery was assessed and number of tyrosine hydroxylase (TH)-positive neurons in substantia nigra (SN) was analyzed. Tumor necrosis factor receptor-associated factor 1(TRAF1), P-Akt and Bcl-2/Bax were determined in mesencephalic tissue by Western blot method. PC12 cells and primary cultured mesencephalic neurons were employed to further investigate the mechanism of Aceglutamide. RESULTS: Aceglutamide treatment improved behavioral functions, reduced the infarction volume, and elevated the number of TH-positive neurons in the SN. Moreover, Aceglutamide significantly attenuated neuronal apoptosis in the SN. Meanwhile Aceglutamide treatment significantly inhibited the expression of TRAF1 and up-regulated the expression of P-Akt and Bcl-2/Bax ratio both in vitro and in vivo. CONCLUSIONS: Aceglutamide ameliorated motor dysfunction and delayed neuronal death in the SN after ischemia, which involved the inhibition of pro-apoptotic factor TRAF1 and activation of Akt/Bcl-2 signaling pathway. These data provided experimental information for applying Aceglutamide to ischemic stroke treatment.

Changes and overlapping distribution in the expression of CB1/OX1-GPCRs in rat hippocampus by kainic acid-induced status epilepticus.

Status epilepticus (SE) is a life-threatening neurological disorder. It is important to discover new drugs to control SE without the development of pharmacoresistance. Focus on the cannabinoid receptor and cannabinoid-related compounds might be a good option. Cannabinoid receptor 1 (CB1) and orexin receptor 1 (OX1) both belong to the GPCR superfamily and display "cross-talk" interactions, however, there has been no study of the effect of OX1/CB1 in epilepsy. Therefore, we investigated the potential long-term effects of SE on CB1 and OX1 expression in rat hippocampus, aiming to elucidate whether they are involved in the causative mechanism of epilepsy and whether they might form a heterodimer. In this study, SE was induced with kainic acid, and results of immunohistochemistry and RT-PCR both showed that the expression of CB1 in the hippocampus increased after SE and was significantly higher compared to controls especially 1 week post-SE. However we did not find any significant difference in the expression of OX1 between the SE group and the controls at any time. Under immunofluorescence staining, we observed an overlapping distribution of CB1 and OX1 in the hippocampus. The increased expression of CB1 in the hippocampus indicates that CB1 may play an important role in the underlying mechanism of SE, but the effect of OX1 was not obvious. The overlapping distribution of CB1 and OX1 in the hippocampus indicates that they may form a heterodimer to exert their effect in epilepsy.

Propofol may protect PC12 cells from ß-amyloid25₋35 induced apoptosis through the GSK-3ß signaling pathway.

BACKGROUND: There are two major pathological hallmarks of Alzheimer's disease. One is the progressive accumulation of beta-amyloid (Aß) in the form of senile plaques; the other is hyperphosphorylated tau, causing neuronal apoptosis. Some inhalation anesthetics, such as isoflurane and desflurane, have been suggested to induce Aß accumulation and cause AD-like neuropathogenesis. Whether intravenous anesthetics have similar effects is still unclear. We therefore set out to determine the relationship between propofol and AD-like pathogenesis. METHODS: PC12 cells were cultured in serum-free medium for 12 hours prior to drug treatment. Various concentrations from 5 µmol/L to 80 µmol/L of aggregated Aß25-35 were added to determine a proper concentration for further study. After exposure to 10 µmol/L Aß25-35 alone or with 20 µmol/L propofol for 6 hours, PC12 cell viability was determined by MTT assay. Western blotting and immunocytochemical staining were performed to observe the protein expression of the Bcl-2 family, tau phosphorylation at different sites, and tau protein kinases and phosphatases. RESULTS: Aß25-35 induced a decrease in PC12 cell viability in a dose-dependent manner. Exposure to 10 µmol/L Aß25-35 for 6 hours resulted in the mild cell survival, accompanied by a decline in Bcl-2, and an increase in phosphorylation of GSK-3ß and tau at different sites. Compared with the Aß25-35 group, cells treated with propofol alone showed no significant difference, while cells co-incubated with propofol and Aß25-35 showed a significantly higher survival rate (P < 0.01 or P < 0.05). Tau phosphorylation at Ser396, Ser404 and Thr231 and the level of GSK-3ß in PC12 cells increased after exposure to 10 µmol/L Aß25-35. Co-incubation with propofol attenuated cellular apoptosis by inhibiting tau phosphorylation. CONCLUSIONS: These data indicate that propofol may protect PC12 cells from Aß25-35-induced apoptosis and tau hyperphosphorylation through the GSK-3ß pathway, therefore it may be a safer anesthesia for AD and elderly patients.

Fabrication of biocompatible and mechanically reinforced graphene oxide-chitosan nanocomposite films.

BACKGROUND: Graphene oxide (GO)can be dispersed through functionalization, or chemically converted to make different graphene-based nanocomposites with excellent mechanical and thermal properties. Chitosan, a partially deacetylated derivative of chitin, is extensively used for food packaging, biosensors, water treatment, and drug delivery. GO can be evenly dispersed in chitosan matrix through the formation of amide linkages between them, which is different from previous reports focusing on preparing GO/chitosan nanocomposites through physical mixing. RESULTS: In this study, free-standing graphene oxide-chitosan (GO-chitosan) nanocomposite films have been prepared. The GO-chitosan films are biologically compatible and mechanically reinforced. Through the formation of amide linkages between GO's carboxylic acid groups and chitosan's amine groups, GO could be evenly dispersed within the chitosan matrix. We also characterized the GO-chitosan composite films using element analysis, Fourier transform infrared spectroscopy, X-ray photo electron spectroscopy, differential scanning calorimetry, and thermo gravimetric analysis. Compared to pristine chitosan film, the tensile strength of GO-chitosan film is improved by 2.5 folds and Young's modulus increases by nearly 4.6 folds. The glass transition temperature of GO-chitosan composite film shifts from 118°C to 158°C compared to the pristine chitosan, indicating its enhanced thermal stability. GO-chitosan composite film was also evaluated for its biocompatibility with C3H10T1/2 cells by in vitro fluorescent staining. The graphene oxide-reinforced chitosan composite films could have applications in functional biomaterials. CONCLUSION: The present study describes a useful and simple method to chemically attach biocompatible chitosan onto graphene oxide. We envision that the GO-chitosan film will open avenues for next-generation graphene applications in the realm of functional biomaterial.

Neural regeneration: role of traditional Chinese medicine in neurological diseases treatment.

The effects of a single compound and a mixture of traditional Chinese medicine (TCM) on promoting proliferation, differentiation, and migration of neural stem cells and regulating their microenvironment have been observed by Chinese scholars in recent years. These results showed good prospects in improving neural regeneration and repair of neurological disorders such as ischemic brain injury, Alzheimer's disease, Parkinson's disease, and depression. According to the TCM theory, the relationship between life of an individual and the disease was regarded as an entirety, and the theory emphasized the treatment based on syndrome differentiation since ancient times. In this paper, we attempted to introduce these medicines, which belong to natural products and have already been proved to possess clear therapeutic action on human bodies in the clinical setting. We summarized their effects promoting brain neurogenesis and repairing brain injuries in animal models and some mechanisms at the cellular and molecular levels.

Gossypium herbaceam L. extracts ameliorate disequilibrium of IL-1RA/IL-1ß ratio to attenuate inflammatory process induced by amyloid ß in rats.

A chronic inflammatory response possibly mediated by Amyloid ß (Aß) is believed to be a major factor in the pathology of Alzheimer's disease (AD). Studies suggest that the mediators of the inflammatory response, which might contribute to brain damage, involve cytokines, such as IL-1ß. IL-1ß could play an important part in the development of pathologic conditions. There is also an endogenous interleukin-1 receptor antagonist (IL-1RA) in IL-1 family, which could prevent the actions of IL-1ß by competing for receptor binding without inducing any signal transduction. Therefore, the balance of IL-1ß vs IL-1RA is a critical parameter in determining not only whether excessive host inflammation will occur, but also the degree of subsequent host cell damage and associated toxicity. In our previous study, it has been determined that the anti-inflammatory action of Gossypium herbaceam L. extracts (GHE) was involved in its neuroprotection. However, the effects of GHE on IL-1ß and IL-1RA have not been clearly defined in the experimental rat model of AD induced by Aß. Therefore, the current study is performed to evaluate whether GHE could affect the disequilibrium of IL-1RA/IL-1ß ratio in the hippocampus of rats after Aß treatment. Subsequently, we further identify that GHE could efficaciously promote Akt and GSK3ß phosphorylation, and thereby contribute to IL-1ß release decrease as well as a concurrent increase in the level of IL-1RA through NF-κB and MAPK pathways. As a consequence, GHE is potentially beneficial to maintain the endogenous IL-1RA/ IL-1ß balance in the hippocampus of rats and it might be a potential agent to ameliorate inflammatory process in AD.

Antinociceptive effects of combination of tramadol and acetaminophen on painful diabetic neuropathy in streptozotocin-induced diabetic rats.

OBJECTIVE: The purpose of this study was to establish the streptozotocin (STZ)-induced diabetic model with rats and investigate the antinociceptive effect of combination of Tramadol (TR) and Acetaminophen (NAPA) on the animal model for the first time. METHODS: Diabetic model was induced by a single injection of STZ (60 mg/kg, intraperitoneal). Nociceptive thresholds were measured by means of electronic von Frey test, hot-plate test, and tail-flick test. On the 28th day of diabetes induction, diabetic rats with significant hyperalgesia were randomly divided into three groups: TR, NAPA, and TR-NAPA combination group. Each group was randomly divided into four subgroups. Three geometric series of drugs were given to each group respectively. Antinociceptive effects of the drugs were assessed at 15, 30, 60, 120, and 180 minutes after drug administration. 50% Maximum antinociceptive effect of each drug was determined by probit analysis, whereas interaction between TR and NAPA was evaluated by isobolographic analysis. RESULTS: Hyperalgesia, along with hyperglycemia, developed 4 days after STZ injection and persisted at all tested time points until 28 days. TR, NAPA, and TR-NAPA combination administration all produced dose-dependent antinociceptive effects. Isobolographic analysis showed a significant deviation of TR/NAPA 50% maximum antinociceptive effect (in tail-flick test, but not in von Frey test) from the additive line. CONCLUSIONS: Combination of the two drugs produces an additive antinociceptive effect in tail-flick test, whereas probable additive antinociceptive effect in von Frey test in painful diabetic neuropathy rats.

Analgesic effect of gabapentin in a rat model for chronic constrictive injury.

BACKGROUND: Gabapentin has been widely and successfully used in the clinic for many neuropathic pain syndromes since last decade, however its analgesic mechanisms are still elusive. Our study was to investigate whether Ca(2+)/calmodulin-dependent protein kinase II (CaMKII) contributes to the analgesic effect of gabapentin on a chronic constriction injury (CCI) model. METHODS: Gabapentin (2%, 100 mg/kg) or saline (0.5 ml/100 g) was injected intraperitoneally 15 minutes prior to surgery and then every 12 hours from postoperative day 0 - 4 to all rats in control, sham and CCI groups. The analgesic effect of gabapentin was assessed by measuring mechanical allodynia and thermal hyperalgesia of rats. Expression and activation of CaMKII were quantified by reverse-transcriptional polymerase chain reaction and Western blotting. RESULTS: The analgesic effect of gabapentin on mechanical allodynia and thermal hyperalgesia was significant in the CCI model, with maximal reduction reached on postoperative day 8. Gabapentin decreased the expression of the total CaMKII and phosphorylated CaMKII in CCI rats. CONCLUSION: The analgesic effect of gabapentin on CCI rats may be related to the decreased expression and phosphorylation of CaMKII in the spinal cord.

[Relationship of oxidative DNA damage and expression of mitochondrial apoptotic proteins in rat striatum induced by 6-hydroxydopamine].

OBJECTIVE: To study the relationship between oxidative DNA damage and mitochondrial apoptosis relative proteins in rat striatum induced by 6-hydroxydopamine (6-OHDA) during the pathogenesis of Parkinson's disease (PD). METHODS: 6-OHDA was stereotactically injected into the bilateral right striatum of rats to produce PD models. Assays for 8-oxo-dG immunohistochemistry and Western blot for MTH1, Cytochrome c, Cl-caspase 9 and Cl-caspase 3 in right striatum was separately conducted. RESULTS: In 10 successful PD rats, compared with either sham or normal group, there were obvious more 8-oxo-dG positive cells in lesioned striatum while there was a lower expression of MTH1. Furthermore, the expressions of such intrinsic apoptotic pathway factors as cytoplasmic Cytochrome c, Cl-caspase 9 and Cl-caspase 3 were highly up-regulated in lesioned striatum. CONCLUSION: Oxidative DNA damage plays a key role in the pathogenesis of PD. Furthermore Cytochrome c, caspase 9 and caspase 3 are involved in the regulation of apoptosis under oxidative DNA damage induced by 6-OHDA.

Protective effects of octacosanol on 6-hydroxydopamine-induced Parkinsonism in rats via regulation of ProNGF and NGF signaling.

AIM: To investigate the protective effects of octacosanol in 6-hydroxydopamine-induced Parkinsonian rats and find whether octacosanol has effects on pro nerve growth factor (pro-NGF), NGF and the downstream effector proteins. METHODS: Behavioral tests, enzymatic assay, tyrosine hydroxylase immunohistochemistry, TUNEL and Western blot were used to investigate the effects of octacosanol in this rat model of PD. RESULTS: Oral administration of octacosanol (35-70 mg/kg, po for 14 d) significantly improved the behavioral impairments in rats induced by 6-OHDA and dose-dependently preserved the free radical scavenging capability of the striatum. Octacosanol treatment also effectively ameliorated morphological appearances of TH-positive neuronal cells in nigrostriatal systems and decreased the apoptotic cells induced by 6-OHDA in striatum. In addition, octacosanol strikingly blocked the 6-OHDA-induced increased expression of proNGF-p75NTR-sortilin death signaling complex and its downstream effector proteins. Meantime, octacosanol prevented the decreased levels of NGF, its receptors TrkA and p-Akt which together mediated the cell survival pathway. CONCLUSION: The findings implicated that the anti-parkinsonism effects afforded by octacosanol might be mediated by its neuro-microenvironment improving potency through retrieving the ratios of proNGF:NGF and the respective receptors p75NTR:TrkA in vivo. Due to its excellent tolerability and non-toxicity, octacosanol may be a promising agent for PD treatment.

Age-related alterations in the expression of MTH2 in the hippocampus of the SAMP8 mouse with learning and memory deterioration.

MutT-related proteins degrade 8-oxo-7,8-dihydrodeoxyguanosine triphosphate (8-oxo-dGTP), a mutagenic substrate for DNA synthesis in the nucleotide pool, thereby preventing DNA replication errors. MTH2 (Mut T homolog 2), which belongs to this family of proteins, possesses 8-oxo-7,8-dihydro-2'-deoxyguanosine triphosphatase (8-oxo-dGTPase) activity and appears to function in the protection of the genetic material from the untoward effects of endogenous oxygen radicals. To examine the roles of MTH2 in the aging process, we used the senescence-accelerated prone mouse 8 (SAMP8), which exhibits early aging syndromes and declining abilities of learning and memory. Immunohistochemical and western blot analysis revealed that the level of MTH2 protein in the hippocampus of the SAMP8 mouse progressively decreases beginning from four months after birth, whereas no such change was observed in the control senescence-accelerated resistant mouse 1 (SAMR1). Under these conditions, 8-oxoguanine accumulates in the nuclear DNA in the CA1 and CA3 subregions of the hippocampus of SAMP8 in an age-dependent manner. In SAMR1 mice, accumulation of 8-oxoguanine in the DNA was not observed. These results suggest that the MTH2 deficiency might be one of the causative factors for accelerated aging.

Effects of hormone replacement therapy on magnetic resonance imaging of brain parenchyma hyperintensities in postmenopausal women.

AIM: To apply 3.0 magnetic resonance imaging (MRI) to study the effects of long-term, low dose hormone replacement therapy (HRT) on the brain parenchyma of postmenopausal women. METHODS: A total of 155 postmenopausal healthy female medical staff members from Peking Union Medical College Hospital were enrolled. The HRT group was composed of 71 subjects who had been given a low dose of HRT for over 4 years, while 84 women who had never been given HRT were enrolled in the control group. The Mini-Mental State Examination (MMSE) was used to evaluate mental state, and an Enzyme-Linked ImmunoSorbent Assay (ELISA) was used to detect plasma levels of sex hormones. In addition, all participants were subjected to an MRI, including axial T2 weighted imaging (T2WI), fluid-attenuated inversion recovery (FLAIR), T1 weighted imaging (T1WI, oblique coronal, vertical to the hippocampus, slice thickness 3 mm without gaps), and a 3D image of the whole brain. RESULTS: The ELISA showed that the plasma level of estradiol in the HRT group was significantly higher than that in the control group (P<0.05). No differences were observed in the MMSE between the two groups. In participants older than 70 years of age, the number of deep white matter hyperintensities (DWMHs) in the control group was significantly higher than that in the HRT group (P=0.0013); however, in other age subgroups, no statistical differences were observed. Finally, no significant difference in periventricular hyperintensity (PVH) between the two groups was observed. CONCLUSION: We found that a high plasma level of estradiol in postmenopausal women receiving long-term HRT was correlated with the survival of brain parenchyma.Acta Pharmacologica Sinica (2009) 30: 1065-1070; doi: 10.1038/aps.2009.81.

Gossypium herbaceam extracts attenuate ibotenic acid-induced excitotoxicity in rat hippocampus.

Excitotoxicity is one of the most extensively studied processes of neuronal death and plays an important role in Alzheimer's disease. In the present study, the protective effects of Gossypium herbaceam extracts (GHE) on learning and memory impairment induced by excitatory neurotoxin ibotenic acid were examined in vivo using Morris water maze. Furthermore, neuroprotective effects of GHE were investigated with methods of immunohistochemistry and biochemistry. Our data showed that oral administration with GHE at the doses of 35, 70 and 140 mg/kg exerted an improved effect on the learning and memory impairment in rats induced by intracerebral injection of ibotenic acid. To confirm the precise mechanism of memory improvement by presence of GHE, we further investigated the potential protection on the hippocampus. Our findings suggest that GHE afforded a beneficial inhibition on pro-apoptosis proteins expression following ibotenic acid. Additionally, calcium pump activity and calbindin-D28k expression were dramatically increased after GHE treatment, implicating that the modulation of calcium homeostasis could be involved in the mechanism underlying neuroprotection of GHE against ibotenic acid-induced excitotoxicity. These data suggested that GHE could be a potential agent for preventing or retarding the development or progression of Alzheimer's disease.

Gossypium herbaceam extracts inhibited NF-kappaB activation to attenuate spatial memory impairment and hippocampal neurodegeneration induced by amyloid-beta in rats.

Amyloid-beta (Abeta) is considered to be responsible for the pathogenesis of Alzheimer's disease. In the present study, the protective effect of Gossypium herbaceam extracts (GHE) on learning and memory impairment induced by Abeta were examined in vivo using Morris water maze and step through task. Furthermore, the antioxidant activity and neuroprotective effect of GHE was investigated with methods of histochemistry and biochemistry. These data showed that oral administration with GHE at the doses of 35, 70 and 140 mg/kg exerted an improved effect on the learning and memory impairment in rats induced by intracerebroventricular (i.c.v.) injection of 10 microg of Abeta(25-35). Subsequently, the GHE afforded a beneficial action on promotion on the activity of glutathione peroxidase and catalase, as well as inhibition on the NF-kappaB activation in the hippocampus followed by the presence of Abeta(25-35). Meanwhile, the number of degenerating neurons with an apoptotic feature was dramatically decreased in hippocampus after treatment with GHE, implicating that its antioxidant stress and inhibition of NF-kappaB activation could be involved in the mechanism underlying neuroprotection of GHE against Abeta-induced cell death. These findings suggested that GHE might be a potential agent for treatment of Alzheimer's disease.

Effects of long-term low-dose hormone replacement therapy on the binding capacity of platelet peripheral-type benzodiazepine receptor in postmenopausal women.

The effects of long-term low-dose hormone replacement therapy (HRT) on the level of hormone in plasma and on the binding capacity of peripheral-type benzodiazepine receptor (PBR) on the platelet membranes were investigated among women. This study was a retrospective and case-controlled study where 64 women using long-term low-dose HRT for over 4 years entered the study and 99 women, age and education matched, were enrolled as control. Plasma hormone level and platelet PBR binding capacity of two groups were analyzed. A significant increase in plasma estradiol level in women using HRT was observed, compared to those in the control group. Meanwhile, women in the HRT group displayed higher platelet PBR binding capacity. Further analysis demonstrated that the binding capacity of platelet PBR was closely related to estradiol plasma level in all subjects. These results suggest that long-term low-dose HRT could relieve the decrease of estradiol level in plasma and PBR binding capacity on platelets in postmenopausal women, alleviate the endocrine imbalance process, and might be beneficial for reducing the risks of some diseases.

Transplantation of human amniotic cells exerts neuroprotection in MPTP-induced Parkinson disease mice.

To determine the survival and differentiation of cultured Human amniotic cells (HACs) upon transplantation into the brain of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson disease (PD) mice. Mouse model of PD was established with injections of MPTP (15 mg/kg, fourth, 2 h interval). After being labeled with PKH26, HACs isolated from human were transplanted into the striatum of PD mice. Immunohistochemistry was performed to evaluate the toxicity of MPTP in the substantia nigra, graft survival and endogenous neurogenesis. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) level in the striatum were tested by ELISA. Our results showed that cultured HACs can express the marker of neural progenitor cells and differentiate into neuron, dopaminergic neuron, astrocyte and oligodendrocyte. TH-positive neural cells were significantly reduced in the substantia nigra in the model mice, whereas which increased in transplantation mice. Immunohistology results showed that transplanted HACs survived and migrated in the brain of PD model mouse, though no morphological integration was observed. BrdU-positive cells in the Subventricular zone (SVZ) and neurotrophins of the striatum increased in the transplantation mice. The results suggested that transplanted HACs could survive and promote the endogenous neurogenesis of mice, which maybe related to the increased level of neurotrophins of the striatum.